Williams took out one, Varvara Lepchenko, in a 1-hour 35-minute match on Ashe Stadium court that was hard fought and a testimonial to how tough the 33-year-old Williams still is. Top-seeded Serena got peppered with 24 winners from the left-handed Lepchenko, of Allentown, Pa., but had 11 fewer unforced errors and won, 6-3, 6-3.

Earlier, 11th-seeded Flavia Pennetta of Italy had defeated Nicole Gibbs, 6-4, 6-0. Gibbs is 21, from Santa Monica, and turned pro last year after winning her second straight NCAA singles title at Stanford.

Then, in short order, the last two U.S. men left went down. Sam Querrey lost on Ashe to No. 1 Novak Djokovic, 6-3, 6-2, 6-2, and John Isner was eliminated for the third year in a row at this event by German Philipp Kohlschreiber. The score was 7-6 (4), 4-6, 7-6 (2), 7-6 (4), an especially shocking result because big servers such as Isner usually hold the upper hand in tiebreakers.

"It's very disappointing," Isner said. "I need to be better than that. I am better than that. I'm disappointed for me personally. Not for America as a whole. I don't think about that."

Isner hit 42 aces and 77 winners (aces are included in winners) and still lost. Isner was seeded 13th, Kohlschreiber 22.

The biggest upset of the day was that of second-seeded, Wimbledon champion Petra Kvitova. She lost to a qualifier, No. 145 Aleksandra Krunic of Serbia, 6-4, 6-4.

Other winners of note, making advances to the fourth round, were No. 8 and former champion Andy Murray, who defeated Andrey Kuznetsov of Russia, 6-1, 7-5, 4-6, 6-2; and No. 5 Canadian Milos Raonic, who defeated Victor Estrella Burgos of the Dominican Republic, 7-6 (5), 7-6 (5), 7-6 (3).

No. 3 Stan Wawrinka got through in a walkover.

Williams, who can win an 18th major title with a victory here, which would also be her sixth U.S. Open title, said she is not taking anything for granted, because she has failed to reach the quarterfinals this year of any of the previous Grand Slam events.

"I've been a casualty this whole year at Grand Slams," she said. "I'm just hoping to keep staying in there."

Williams will next play No. 50 Kaia Kanepi of Estonia. Kanepi, who took out former champion Samantha Stosur in the second round, beat Carla Suarez-Navarro of Spain, seeded No. 15, 7-5, 6-0.

The recent story of Chicago's Jackie Robinson West Little League team, their U.S. title taken away because some of their players lived outside the district they represented, struck a nerve with Phil Hart.

The 24 trades made Monday that moved 43 players in the hours before the NHL trading deadline were more strategic than splashy, nothing that justified the hype that has grown around this annual day of reckoning and nothing that will immediately transform a franchise.